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Photochemical Properties and Structure–Activity Relationships of Ru II Complexes with Pyridylbenzazole Ligands as Promising Anticancer Agents
Author(s) -
Havrylyuk Dmytro,
Heidary David K.,
Nease Leona,
Parkin Sean,
Glazer Edith C.
Publication year - 2017
Publication title -
european journal of inorganic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.667
H-Index - 136
eISSN - 1099-0682
pISSN - 1434-1948
DOI - 10.1002/ejic.201601450
Subject(s) - chemistry , cytotoxicity , ruthenium , photodynamic therapy , prodrug , irradiation , ligand (biochemistry) , photochemistry , stereochemistry , visible spectrum , combinatorial chemistry , receptor , in vitro , biochemistry , organic chemistry , catalysis , physics , nuclear physics , optoelectronics
Ruthenium complexes capable of light‐triggered cytotoxicity are appealing potential prodrugs for photodynamic therapy (PDT) and photoactivated chemotherapy (PACT). Two groups of (polypyridyl)Ru II complexes with 2‐(2‐pyridyl)benzazole ligands were synthesized and investigated for their photochemical properties and anticancer activity to compare strained and unstrained systems that are likely to have different biological mechanisms of action. The structure–activity relationship was focused on the benzazole‐core bioisosterism and replacement of coligands in Ru II complexes. Strained compounds rapidly ejected the 2‐(2‐pyridyl)benzazole ligand after light irradiation, and possessed strong toxicity in the HL‐60 cell line both under dark and light conditions. In contrast, unstrained Ru II complexes were nontoxic in the absence of light, induced cytotoxicity at nanomolar concentrations after light irradiation, and were capable of light‐induced DNA damage. The 90–220‐fold difference in light and dark IC 50 values provides a large potential therapeutic window to allow for selective targeting of cells by exposure to light.